HivARCHNCT06016114
Analysis of the Reservoir in Individuals Controlling HIV Infection
An observational study of Hiv, run by University Hospital, Ghent.
Trial summary
The aim of this study is the gain new insights into HIV latency in HIV controllers through extensive blood an tissue sampling (lymph node, colon biopsies, placenta) from 25 individuals living with HIV and healthy individuals. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hiv
- What is being tested?
- HIV Latency Diagnostic Sampling
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2024to 1 Oct 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HIV-positive individuals (pregnant and non-pregnant) and pregnant HIV-negative individuals
Who may be able to join
- Elite Controllers: pVL<50 copies per ml for at least 12 months, treatment naive at the time of inclusion
- Viral controllers: pVL <2000 copies/ml; CD4>500/µL for at least two years, treatment naïve at the time of inclusion
- Long-term non-progressors: CD4>500/µL, pVL <10000 copies/ml, for at least 7 years, treatment naïve at the time of inclusion
- Post treatment controllers: on cART for at least 12 months; pVL <500 copies/ml for at least 2 years after treatment cessation .
- PLWH who received bone marrow transplant: people living with HIV who received a bone-marrow transplant for non-HIV related reasons
Who cannot join
- Current history of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification), consisting of chronic HIV-1 infection.
- Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (= HBV antigen or viral load negative and positive HBV surface antibody)).
- Evidence of active HCV infection (HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry).
- Current or known history of cardiomyopathy or significant ischemic or cerebrovascular disease.
- Current history of cancer.
- History of HIV-related thrombocytopenia.
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- Any condition, including preexisting psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant.
- Abnormal results of standard of care laboratory tests:
- Confirmed haemoglobin <11g/dl for women and <12 g/dl for men
- Confirmed platelet count <100 000/µl *
- Confirmed neutrophil count <1000/μl
- Confirmed AST and/or ALT >10xULN
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry.
- The following treatment will be prohibited three months before screening and during the study:
- immunosuppressive drugs (inclusive corticosteroids) except for drugs used for topical use.
- Immunomodulatory drugs including but not limited to Granulocyte-colony stimulating factors, Granulocyte-monocyte colony-stimulating factor, interleukin 2, 7 \& 15.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The aim of this study is the gain new insights into HIV latency in HIV controllers through extensive blood an tissue sampling (lymph node, colon biopsies, placenta) from 25 individuals living with HIV and healthy individuals.
- Conditions
- Hiv
- Being tested
- HIV Latency Diagnostic Sampling
- Keywords
- HIV, Latency
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIV Latency Diagnostic SamplingDiagnostic test
This intervention involves the collection of blood, lymph node, colon biopsy, and placental samples from individuals living with HIV (HIV controllers) and healthy controls. The goal is to investigate HIV latency by analyzing these biological samples to gain insights into the mechanisms and characteristics of latent HIV reservoirs. The sampling procedures will be conducted using minimally invasive techniques where appropriate, and the collected samples will undergo laboratory analysis for further study.
| Study group | Role | What they receive |
|---|---|---|
| HIV-1 positive individuals (non-pregnant) | Not described Receives: Diagnostic Test: HIV Latency Diagnostic Sampling | |
| Pregnant HIV-1 positive/negative individuals | Not described Receives: Diagnostic Test: HIV Latency Diagnostic Sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of total and intact HIV DNA and HIV RNA
Rainbow assay: multiplex digital PCR approach that combines five different HIV-1 regions to quantify total HIV-1 DNA and intact HIV-1 DNA simultaneously (Qiacuity dPCR platform, Qiagen).
mutliplex digital PCR approach to quantify HIV RNA
Measured: 5 years
Integration site analysis
HIV/host DNA junctions will be amplified using the Integration Site Loop Amplification (ISLA) assay, and resulting chimeric amplicons will be sequenced by Sanger.
Measured: 5 years
Full-length HIV genome analysis
Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.
Measured: 5 years
Epigenetic analysis
Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)
Measured: 5 years
Matched integration site and proviral sequencing
MIP-seq: captures full-length viral genome sequences in conjunction with its associated viral integration site
Measured: 5 years
Proviral UMI-mediated Long-read Sequencing
HIV-PULSE: characterize the composition of the viral reservoir using long-read sequencing. Involves pre-amplifying individual proviral genomes using PCR and tagging them with dual UMIs, followed by long-range PCR amplification and long-read sequencing on the Oxford Nanopore MinION platform
Measured: 5 years
Transcriptome analysis
- Bulk RNA sequencing on extracted RNA (Illumina Hiseq 2500 with 10-100 ng input of ribodepleted RNA)
- Single cell RNA sequencing (10x genomics technology )
Measured: 5 years
High dimensional phenotyping
CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells
Measured: 5 years
Immunohistochemistry, RNA- and DNA In Situ Hybridization
Immunochemistry will be used to study the expression of activation and exhaustion markers on tissues samples , while viral expression will be assessed through DNAScope and RNAScope technologies
Measured: 5 years
Immunometabolic profile analysis
Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells
Measured: 5 years
Detection of translation-competent reservoirs
HIV-Flow assay: flow cytometry based assay using a combination of 2 antibodies targeting the p24 protein and allowing the detection of cells containing translation-competent viruses. p24+ cells detected by this assay can be sorted for downstream applications and further characterization of translation-competent reservoirs.
The Simultaneous TCR Integration site and Provirus sequencing (STIP-seq) assay will be performed to sequence the proviral genome and matched integration sites of the translation-competent viruses, as well as phenotypic characterization and TCR sequencing of the host cell. characterization of translation-competent reservoirs.
Measured: 5 years
Immunological analysis-FACS
Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using FACS analysis.
Measured: 5 years
Immunological analysis-ELISA
Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using ELISA.
Measured: 5 years
Microbiome monitoring
Gut microbiome will be analyzed in stool and colon biopsies using next-generation sequencing (NGS) of rRNA gene amplicons to identify bacteria at genus/species level
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2023
- Study start1 Dec 2024 (estimated)
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HivStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Linos Vandekerckhove, MD PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06016114
- Sponsor's protocol ID
- ID 12241 - ARCH
- Acronym
- ARCH
- Status last verified
- Sep 2024
- First submitted
- 23 Aug 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of the Reservoir in Individuals Controlling HIV Infection
- ClinicalTrials.gov ID
- NCT06016114
- Acronym / sponsor ID
- ARCH / ID 12241 - ARCH
- Conditions
- Hiv
- Keywords
- HIV, Latency
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 29 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is the gain new insights into HIV latency in HIV controllers through extensive blood an tissue sampling (lymph node, colon biopsies, placenta) from 25 individuals living with HIV and healthy individuals.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV-1 positive individuals (non-pregnant) | – | Diagnostic Test: HIV Latency Diagnostic Sampling |
| Pregnant HIV-1 positive/negative individuals | – | Diagnostic Test: HIV Latency Diagnostic Sampling |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-positive individuals (pregnant and non-pregnant) and pregnant HIV-negative individuals
Key inclusion criteria (5 listed)
- Elite Controllers: pVL<50 copies per ml for at least 12 months, treatment naive at the time of inclusion
- Viral controllers: pVL <2000 copies/ml; CD4>500/µL for at least two years, treatment naïve at the time of inclusion
- Long-term non-progressors: CD4>500/µL, pVL <10000 copies/ml, for at least 7 years, treatment naïve at the time of inclusion
- Post treatment controllers: on cART for at least 12 months; pVL <500 copies/ml for at least 2 years after treatment cessation .
- PLWH who received bone marrow transplant: people living with HIV who received a bone-marrow transplant for non-HIV related reasons
Key exclusion criteria (17 listed)
- Current history of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification), consisting of chronic HIV-1 infection.
- Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (= HBV antigen or viral load negative and positive HBV surface antibody)).
- Evidence of active HCV infection (HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry).
- Current or known history of cardiomyopathy or significant ischemic or cerebrovascular disease.
- Current history of cancer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIV Latency Diagnostic SamplingThis intervention involves the collection of blood, lymph node, colon biopsy, and placental samples from individuals living with HIV (HIV controllers) and healthy controls. The goal is to investigate HIV latency by analyzing these biological samples to gain insights into the mechanisms and characteristics of latent HIV reservoirs. The sampling procedures will be conducted using minimally invasive techniques where appropriate, and the collected samples will undergo laboratory analysis for further study. | Diagnostic test | HIV-1 positive individuals (non-pregnant), Pregnant HIV-1 positive/negative individuals |
Primary outcome
Quantification of total and intact HIV DNA and HIV RNA
Time frame: 5 years
Rainbow assay: multiplex digital PCR approach that combines five different HIV-1 regions to quantify total HIV-1 DNA and intact HIV-1 DNA simultaneously (Qiacuity dPCR platform, Qiagen). mutliplex digital PCR approach to quantify HIV RNA
Integration site analysis
Time frame: 5 years
HIV/host DNA junctions will be amplified using the Integration Site Loop Amplification (ISLA) assay, and resulting chimeric amplicons will be sequenced by Sanger.
Full-length HIV genome analysis
Time frame: 5 years
Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.
Epigenetic analysis
Time frame: 5 years
Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)
Matched integration site and proviral sequencing
Time frame: 5 years
MIP-seq: captures full-length viral genome sequences in conjunction with its associated viral integration site
Proviral UMI-mediated Long-read Sequencing
Time frame: 5 years
HIV-PULSE: characterize the composition of the viral reservoir using long-read sequencing. Involves pre-amplifying individual proviral genomes using PCR and tagging them with dual UMIs, followed by long-range PCR amplification and long-read sequencing on the Oxford Nanopore MinION platform
Transcriptome analysis
Time frame: 5 years
* Bulk RNA sequencing on extracted RNA (Illumina Hiseq 2500 with 10-100 ng input of ribodepleted RNA) * Single cell RNA sequencing (10x genomics technology )
High dimensional phenotyping
Time frame: 5 years
CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells
Immunohistochemistry, RNA- and DNA In Situ Hybridization
Time frame: 5 years
Immunochemistry will be used to study the expression of activation and exhaustion markers on tissues samples , while viral expression will be assessed through DNAScope and RNAScope technologies
Immunometabolic profile analysis
Time frame: 5 years
Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells
Detection of translation-competent reservoirs
Time frame: 5 years
HIV-Flow assay: flow cytometry based assay using a combination of 2 antibodies targeting the p24 protein and allowing the detection of cells containing translation-competent viruses. p24+ cells detected by this assay can be sorted for downstream applications and further characterization of translation-competent reservoirs. The Simultaneous TCR Integration site and Provirus sequencing (STIP-seq) assay will be performed to sequence the proviral genome and matched integration sites of the translation-competent viruses, as well as phenotypic characterization and TCR sequencing of the host cell. characterization of translation-competent reservoirs.
Immunological analysis-FACS
Time frame: 5 years
Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using FACS analysis.
Immunological analysis-ELISA
Time frame: 5 years
Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using ELISA.
Microbiome monitoring
Time frame: 5 years
Gut microbiome will be analyzed in stool and colon biopsies using next-generation sequencing (NGS) of rRNA gene amplicons to identify bacteria at genus/species level
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Linos Vandekerckhove, MD PhD principal investigator
University Hospital, Ghent
Questions about this trial
What is this clinical trial studying?
An observational study of Hiv, run by University Hospital, Ghent.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Klara Dewitte (+32 9 332 06 98, klara.dewitte@ugent.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of total and intact HIV DNA and HIV RNA (time frame: 5 years). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.